11-5698520-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006074.5(TRIM22):c.725G>C(p.Arg242Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,612,768 control chromosomes in the GnomAD database, including 244,870 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.50 (19685 hom., cov: 32)
  • Exomes 𝑓: 0.55 (225185 hom.)
• Consequence: TRIM22 NM_006074.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0650

Genes affected

TRIM22 (HGNC:16379): (tripartite motif containing 22) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to the cytoplasm and its expression is induced by interferon. The protein is involved in innate immunity against different DNA and RNA viruses. [provided by RefSeq, Oct 2021]

TRIM5 (HGNC:16276): (tripartite motif containing 5) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein forms homo-oligomers via the coilel-coil region and localizes to cytoplasmic bodies. It appears to function as a E3 ubiquitin-ligase and ubiqutinates itself to regulate its subcellular localization. It may play a role in retroviral restriction. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.948533E-6).
• BP6: Variant 11-5698520-G-C is Benign according to our data. Variant chr11-5698520-G-C is described in ClinVar as [Benign]. Clinvar id is 2688046.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM22	NM_006074.5	c.725G>C	p.Arg242Thr	missense_variant	4/8	ENST00000379965.8
TRIM22	NM_001199573.2	c.713G>C	p.Arg238Thr	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM22	ENST00000379965.8	c.725G>C	p.Arg242Thr	missense_variant	4/8	1	NM_006074.5	P1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75591 AN: 151940 Hom.: 19677 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.485

GnomAD3 exomes AF: 0.500 AC: 124121 AN: 248092 Hom.: 33067 AF XY: 0.511 AC XY: 68837 AN XY: 134594

Gnomad AFR exome AF: 0.381

Gnomad AMR exome AF: 0.359

Gnomad ASJ exome AF: 0.537

Gnomad EAS exome AF: 0.187

Gnomad SAS exome AF: 0.548

Gnomad FIN exome AF: 0.618

Gnomad NFE exome AF: 0.570

Gnomad OTH exome AF: 0.525

GnomAD4 exome AF: 0.548 AC: 800183 AN: 1460710 Hom.: 225185 Cov.: 48 AF XY: 0.549 AC XY: 398720 AN XY: 726574

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.370

Gnomad4 ASJ exome AF: 0.540

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.543

Gnomad4 FIN exome AF: 0.613

Gnomad4 NFE exome AF: 0.573

Gnomad4 OTH exome AF: 0.531

GnomAD4 genome AF: 0.497 AC: 75624 AN: 152058 Hom.: 19685 Cov.: 32 AF XY: 0.498 AC XY: 37011 AN XY: 74316

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.487

Alfa AF: 0.473 Hom.: 2625

Bravo AF: 0.469

TwinsUK AF: 0.582 AC: 2157

ALSPAC AF: 0.579 AC: 2231

ESP6500AA AF: 0.395 AC: 1598

ESP6500EA AF: 0.570 AC: 4787

ExAC AF: 0.504 AC: 60970

Asia WGS AF: 0.428 AC: 1490 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 63% of patients studied by a panel of primary immunodeficiencies. Number of patients: 60. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	1.5
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0039	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.060	T;T
MetaRNN	Benign	0.0000079	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.038
Sift	Benign	0.036	D;D
Sift4G	Uncertain	0.021	D;D
Polyphen		0.0010	B;B
Vest4		0.076
MPC		0.073
ClinPred		0.011	T
GERP RS		-2.1
Varity_R		0.10
gMVP		0.060

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1063303; hg19: chr11-5719750; COSMIC: COSV66090500; COSMIC: COSV66090500;